Topical Silymarin Administration for Prevention of Capecitabine‐Induced Hand–Foot Syndrome: A Randomized, Double‐Blinded, Placebo‐Controlled Clinical Trial

Abstract

Hand-foot syndrome (HFS) is a frequent dose-limiting adverse reaction of capecitabine in patient with gastrointestinal cancers. Silymarin is a polyphenolic flavonoid extracted from the Silybum marianum that exhibits strong antioxidant and antiinflammatory activities. In this study, we evaluated silymarin efficacy in prevention of capecitabine-induced HFS in patients with gastrointestinal cancers, as the first human study. During this pilot, randomized, double-blinded, placebo-controlled clinical trial, the effect of silymarin gel 1%, which is applied on the palms and soles twice daily starting at the first day of chemotherapy for 9 weeks, on HFS occurrence was assessed. Forty patients fulfilled the inclusion criteria assigned to the silymarin or placebo group. World Health Organization HFS grading scale scores were recorded at baseline and every 3 weeks during these 9 weeks. The median WHO HFS scores were significantly lower in silymarin group at the end of the 9 week (p < 0.05). The scores increased significantly in both placebo and silymarin groups during chemotherapy, but there was a delay for HFS development and progression in silymarin group. Prophylactic administration of silymarin topical formulation could significantly reduce the severity of capecitabine-induced HFS and delays its occurrence in patients with gastrointestinal cancer after 9 weeks of application. Copyright © 2017 John Wiley & Sons, Ltd.

Clinical evidence of prevention strategies for capecitabine‐induced hand‐foot syndrome

“…Of the eligible studies, 12 were RCTs, [9][10][11][12]18,[20][21][22][23][24][25][26] and five were cohort studies. A total of 2081 patients (mean sample size: 122; median sample size with corresponding range: 106 ) were included in this meta-analysis.…”

“…Of the eligible studies, 12 were RCTs, [9][10][11][12]18,[20][21][22][23][24][25][26] and five were cohort studies. [17][18][19]23 The main characteristics of the included studies are shown in Table 1. 11,27 The following prevention strategies were addressed in the analyzed studies: pyridoxine (10 studies) 8,11,12,[19][20][21][22]24,26,27 ; topical urea/ lactic acid (three studies) 8,10,25 ; celecoxib (two studies) 9,28 ; and moisturizing cream, topical silymarin, Fuzheng Jiedusan and neurotropin (four studies).…”

“…[17][18][19]23 Elyasi et al reported that the prophylactic use of topical silymarin significantly reduced severe capecitabine-induced HFS. [17][18][19]23 Elyasi et al reported that the prophylactic use of topical silymarin significantly reduced severe capecitabine-induced HFS.…”

“…17,18 However, neurotropin and moisturizing cream were not effective in preventing HFS. Topical silymarin and Fuzheng Jiedusan may reduce the incidence of capecitabine-induced HFS.…”

Herbal medicine for hand–foot syndrome induced by fluoropyrimidines: A systematic review and meta‐analysis

“…Plenty of traditional herbal formulas have been employed for HFS. The results of RCTs suggest that herbal medicine can alleviate symptoms, relieve pain, and improve QOL (Elyasi, Shojaee, Allahyari, & Karimi, ; Li et al, ; Zhao et al, ). However, no systematic review to date has analyzed the effects of herbal medicine on chemotherapy‐induced HFS.…”